mAb therapy controls CNS-resident lyssavirus infection via a CD4 T cell-dependent mechanism.
EMBO Mol Med
; 15(10): e16394, 2023 10 11.
Article
em En
| MEDLINE
| ID: mdl-37767784
ABSTRACT
Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre-symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti-lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11-dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell-dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ-binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization-independent T cell-mediated effects, even against an established CNS infection by a lethal neurotropic virus.
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Base de dados:
MEDLINE
Assunto principal:
Raiva
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Vírus da Raiva
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Infecções do Sistema Nervoso Central
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Quirópteros
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Infecções por Rhabdoviridae
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Lyssavirus
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article